Dataset Information
Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.
Ontology highlight
ABSTRACT: Objective
The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes.Methods
Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models.Results
Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release by activation of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD), the rate-limiting enzyme for UMP biosynthesis. Adipocyte Xbp1s overexpression drives energy mobilization and protects mice from obesity through activation of the pyrimidine biosynthesis pathway.Conclusion
These observations reveal that Xbp1s is a potent stimulator of uridine production in adipocytes, enhancing lipolysis and invoking a potential anti-obesity strategy through the induction of a futile biosynthetic cycle.
SUBMITTER: Deng Y
PROVIDER: S-EPMC6001360 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Adipocyte Xbp1s overexpression drives uridine production and reduces obesity.
Molecular metabolism 20180302
<h4>Objective</h4>The spliced transcription factor Xbp1 (Xbp1s), a transducer of the unfolded protein response (UPR), regulates lipolysis. Lipolysis is stimulated by fasting when uridine synthesis is also activated in adipocytes.<h4>Methods</h4>Here we have examined the regulatory role Xbp1s in stimulation of uridine biosynthesis in adipocytes and triglyceride mobilization using inducible mouse models.<h4>Results</h4>Xbp1s is a key molecule involved in adipocyte uridine biosynthesis and release ...[more]